Search Results (1,265)

Tissue engineering and regenerative medicine are shifting from passive tissue replacement toward instructive platforms that regulate cellular behavior, immune responses, vascularization, and extracellular matrix remodeling. This review examines recent advances in natural, synthetic, composite, and stimuli-responsive biomaterials, biofabrication and 3D bioprinting, stem and progenitor cell therapies, extracellular vesicles and other cell-free products, immunomodulatory scaffolds, skin organoids and organ-on-a-chip systems, nanotechnology, and artificial intelligence-assisted design. Particular emphasis is placed on plastic, reconstructive, and aesthetic applications, including skin and wound repair, craniofacial bone and cartilage regeneration, peripheral nerve reconstruction, vascularization, and dental and periodontal repair. The review also considers biomodulators and skinboosters as emerging regenerative-aesthetic interventions that aim to improve dermal hydration, fibroblast activity, collagen remodeling, and skin quality rather than provide volume replacement alone. Importantly, these technologies differ substantially in translational maturity, ranging from in vitro and preclinical platforms to early clinical interventions, established clinical products, and commercially available treatments for which durable regenerative efficacy remains incompletely validated. Throughout this review, biological plausibility and preclinical efficacy are therefore distinguished from human clinical evidence, regulatory or established clinical use, and commercial availability. Progress will require standardized characterization, mechanism-linked potency assays, clinically relevant models, and outcome measures that capture functional integration, durability, safety, and aesthetic performance. Full article

Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanocarriers for biomedical applications because of their unique physicochemical properties, including high surface area, large pore volume, excellent drug-loading capacity, controllable biodegradation, and facile surface functionalization. These characteristics have enabled the development of advanced drug delivery systems with enhanced therapeutic efficacy, targeted delivery, improved bioavailability, and reduced systemic toxicity. Recent advances in MSN synthesis, physicochemical properties, surface engineering, and functionalization strategies have significantly improved their biological performance and therapeutic potential. In particular, integrating polymers, lipids, and liposomes with MSN platforms has enhanced colloidal stability, circulation time, cellular uptake, and target specificity, thereby facilitating efficient, stimuli-responsive drug delivery. This review highlights MSN-based drug delivery systems in cancer therapy, where multifunctional nanocarriers enable site-specific delivery, controlled drug release, enhanced tumor accumulation, and reduced off-target effects. The review discusses the expanding roles of MSNs in antimicrobial therapy, wound healing, tissue engineering, and regenerative medicine, emphasizing their ability to promote localized therapeutic delivery, immunomodulation, angiogenesis, and tissue regeneration. The review discusses the diagnostic and theragnostic capabilities of MSNs for disease imaging and monitoring. It also critically evaluates current challenges related to biocompatibility, biodegradation, toxicity, biological barriers, large-scale manufacturing, clinical translation, and regulatory considerations. This review provides a comprehensive overview of recent progress, current limitations, and future opportunities for MSN-based platforms in targeted drug delivery and advanced biomedical applications, supporting their continued advancement toward clinical translation and precision medicine. Full article

Extrusion-based bioprinting imposes stringent mechanical constraints on bioink formulations, yet the rheological parameters governing cell survival during the printing process are rarely reported in a standardized way, limiting cross-study comparison. In this work, we systematically characterized the viscoelastic properties of alginate/methylcellulose bioinks incorporating strontium-enriched hydroxyapatite (Sr-OHAp) particles and Poloxamer 188, and assessed their effect on PANC-1 cell viability in bioprinted constructs. The power law consistency index K and pseudoplasticity index n were used as quantitative descriptors of bioink behavior. Addition of Poloxamer 188 reduced K by 52.1% in particle-free inks and by 64.6% in particle-containing inks, while n remained largely unchanged (≤2% variation), indicating that particles selectively modulate consistency without compromising shear-thinning behavior. On day 1, bioprinted constructs showed lower cell viability than cell-seeded scaffolds (53.9–58.9% vs. 96.7%); however, constructs containing Sr-OHAp (B3) displayed progressive recovery, reaching 84.0% viability by day 7, compared to 72.9% for particle-free bioinks (B1). These results demonstrate that Sr-OHAp particles act as rheological sensitizers that reduce extrusion-induced shear stress while simultaneously promoting long-term cell recovery, likely through their bioactive surface chemistry. We propose that systematic reporting of K and n indices should become standard practice in bioprinting studies to enable rational bioink design and consistent knowledge accumulation across the field. Full article

Localized therapeutic delivery has gained increasing attention as an effective strategy in enhancing treatment efficacy while at the same time minimizing systemic side effects. However, conventional hydrogel-based therapeutic delivery systems often suffer from poor tissue retention and insufficient control over delivery. This drawback is highly pronounced in wet and dynamic biological environments. So, catechol-based adhesive hydrogels have emerged as promising biomaterials for localized therapeutic applications and are inspired by the remarkable wet-adhesion capability of marine mussels. As a highlight, catechol chemistry enables robust tissue adhesion through multiple intermolecular interactions, including hydrogen bonding, metal coordination, and covalent coupling. At the same time, it contributes to hydrogel cohesion and structural stability. Recent advances in hydrogel engineering have expanded the functionality of these systems through integration of injectable formulations, self-healing networks, nanocomposite reinforcement, and stimuli-responsive biointerfaces. These developments have transformed adhesive hydrogels from tissue sealants into multifunctional therapeutic platforms capable of enhancing tissue retention, regulating therapeutic release, and dynamically interacting with biological microenvironments. Here, we review molecular mechanisms underlying catechol-mediated adhesion and discuss recent progress in advanced adhesive hydrogel systems. We further highlight their therapeutic applications in wound healing, musculoskeletal regeneration, exosome and gene delivery, immunomodulatory therapies, and localized cancer therapy. Finally, current translational challenges and future opportunities in developing next-generation smart biointerfaces for precision regenerative medicine are discussed. Full article

Organoids are three-dimensional, stem-cell-derived tissue constructs that recapitulate the architecture and function of native organs, and they have rapidly emerged as transformative tools in regenerative medicine. Their translation from laboratory models to clinical therapies remains constrained, however, by the limitations of conventional culture matrices. Matrigel is the most widely used matrix. It suffers from batch-to-batch variability, an undefined composition, poor mechanical tunability, and a lack of instructive bioactivity. Bioactive ceramics offer a compelling alternative. Encompassing silicate-, phosphate-, and oxide-based formulations, these materials provide controllable ion-release profiles and structural versatility. They also possess a proven capacity to modulate cell behavior through biochemical and biophysical cues. This review systematically examines how the defining properties of bioactive ceramics intersect with the requirements of organoid formation, maturation, and transplantation. We focus on four key properties: ion release, surface bioactivity, mechanical support, and immunomodulation. We survey established and emerging combinations across bone, liver, intestine, biliary, and thyroid organoid systems. Fabrication strategies, including 3D-printed and sol–gel-derived ceramic scaffolds, are also discussed. Finally, we critically assess remaining challenges in vascularization, immune compatibility, and clinical scale-up, and we propose that the deliberate co-design of bioactive ceramics and organoid biology represents a paradigm shift in regenerative medicine. This approach offers a path toward functional, transplantable tissue constructs with genuine therapeutic potential. Full article

The persistent shortage of donor organs and the inherent drawbacks of autologous grafts highlight the urgent need for advanced biomaterial scaffolds in regenerative medicine. Synthetic polymers and animal-derived matrices offer structural support, yet they frequently lack the biological complexity of native tissue or carry translational liabilities—xenogeneic antigens, pathogen transmission risk, and batch variability. This review positions the human placenta as a compelling, ethically sourced, and abundant reservoir for fully human, xeno-free biomaterials. We examine the placenta’s distinct anatomical compartments and their rich complement of extracellular matrix (ECM) proteins, growth factors, and bioactive cytokines. These components confer potent pro-angiogenic, anti-inflammatory, antimicrobial, and immunomodulatory properties, enabling precise direction of cellular behavior and tissue regeneration. We systematically assess recent advances in decellularization and the processing strategies required to preserve these bioactivities while eliminating immunogenic material. By integrating current tissue engineering applications with the regulatory and ethical frameworks shaping clinical translation, we argue that placenta-derived matrices are uniquely positioned to transcend the limitations of conventional scaffolds and serve as a robust platform for future regenerative therapies. Full article

Cranial bone defects remain a significant clinical challenge due to their limited intrinsic regenerative capacity and the complexity of coordinating osteogenesis, angiogenesis, and immune responses within a confined and poorly vascularised environment. Conventional approaches, including autologous grafts and synthetic implants, provide structural support but fail to actively modulate the biological processes required for effective bone regeneration. In this context, hydrogel-based systems have emerged as versatile platforms for localized and controlled drug delivery in cranial bone tissue engineering (BTE). This review provides a comprehensive overview of hydrogel-based delivery strategies designed to regulate the spatiotemporal presentation of bioactive agents within cranial defects. The main classes of hydrogels, natural, synthetic, semi-synthetic, and hybrid systems, are discussed in relation to their physicochemical properties and suitability for drug delivery applications. Current delivery approaches are analysed, including cell-free systems (growth factors, peptides, bioactive ions, nucleic acids, and small molecules drugs), cell-based platforms, and multifunctional systems integrating secondary carriers such as nanoparticles (NPs), microparticles (MPs), and extracellular vesicles (EVs). Particular emphasis is placed on how hydrogel design parameters, including crosslinking density, degradation kinetics, and responsiveness to microenvironmental cues, govern therapeutic release and influence regenerative outcomes. Emerging strategies and key translational challenges are also highlighted. Full article

Mesenchymal stromal cells (MSCs) are a versatile platform for regenerative medicine and gene delivery because they combine multipotency, immunoregulatory activity, and injury-directed trafficking. Translation is nevertheless limited by donor- and tissue-dependent heterogeneity, variable biodistribution, and engineering-related risks. This review evaluates genetically modified MSCs as medicinal products rather than as a general MSC class. We compare self-inactivating lentiviral (SIN-LV) transduction, which provides efficient and durable expression and has limited early clinical experience, with targeted genome editing, which can define the integration locus and copy number but remains constrained by variable precise knock-in efficiency, off-target and double-strand-break-associated effects, manufacturing cost, and the absence of long-term clinical safety data. We integrate preclinical and clinical evidence with GMP-compatible manufacturing, potency testing, genomic surveillance, and release criteria. Particular attention is given to safe-harbor integration and B2M/CIITA-based hypoimmunogenic designs as strategies to reduce engineering-related batch variability and HLA-dependent donor variability. Together, these developments support a transition from empirically optimized MSC preparations toward molecularly defined cellular medicines with predefined genotype, expression, potency, and safety attributes. Full article

Three-dimensional (3D) bioprinting has emerged as a versatile biofabrication strategy that enables the precise, spatiotemporally controlled co-deposition of living cells, biomaterials, and bioactive agents, including growth factors, cytokines, and extracellular matrix (ECM) components, into geometrically defined 3D constructs. By translating digital design models derived from computed tomography (CT), magnetic resonance imaging (MRI), or computational modeling directly into physical tissue architectures, 3D bioprinting facilitates the assembly of hierarchically organized constructs that closely recapitulate the structural, mechanical, and functional characteristics of native tissues. The principal 3D bioprinting strategies are broadly classified into scaffold-based and scaffold-free approaches. Engineered bioinks, whether formulated as cell-laden natural, synthetic, or composite polymer hydrogels, tissue-derived decellularized ECM (dECM) components, or pure cellular spheroids and organoids, constitute the cornerstone of these biofabrication platforms. Scaffold-based 3D bioprinting comprises extrusion-based, droplet-based (inkjet and drop-on-demand), light-based vat photopolymerization (stereolithography and digital light processing), and laser-assisted bioprinting based on laser-induced forward transfer (LIFT). Each of these modalities imposes distinct constraints on bioink rheology, crosslinking mechanisms, spatial resolution, throughput, and post-printing cell viability; consequently, a specific 3D bioprinting strategy is selected according to the specific requirements of the target tissue application. Scaffold-free 3D bioprinting and bioassembly techniques, including the Kenzan method, aspiration-assisted bioprinting, magnetic bioprinting, and other field-directed tissue assembly approaches, enable the fabrication of spheroid- and organoid-based constructs without the necessity for exogenous biomaterial scaffolds. Because native tissues exhibit diversity in cellular composition, ECM architecture, mechanical properties, and physiological function, no individual bioprinting platform or bioink formulation serves as a universal 3D bioprinting solution. The engineering of biomimetic tissue constructs, therefore, requires the selection of application-tailored fabrication approaches. Under this biofabrication paradigm, 3D bioprinting has been applied across a wide range of tissue engineering targets, including skin, bone, cartilage, osteochondral interfaces, cardiac and vascular tissue, neural structures, ocular, dental, and adipose tissue. This review discusses recent advances in scaffold-based and scaffold-free 3D bioprinting applications for tissue engineering and regenerative medicine across diverse tissue systems. Full article

Pullulan, a natural microbial polysaccharide composed of repeating maltotriose units, is widely explored as a candidate for advanced cell culture configurations, tissue engineering (TE), and regenerative medicine (RM). Due to its excellent biocompatibility, lack of immunogenicity, and structural flexibility, it serves as a versatile base material. Pristine pullulan exhibits high water solubility and lacks intrinsic signals for cell attachment and proliferation. However, the presence of nine reactive hydroxyl groups per repeating maltotriose unit enables extensive chemical functionalization to address these limitations. This review provides a comprehensive analysis of multi-functional design strategies used to tailor pullulan into distinct structural forms, such as hydrogels, porous scaffolds, electrospun fibrous membranes, thin films, 3D-printed scaffolds, and self-assembling nanosystems. Polymer blending, chemical modification, and crosslinking strategies are discussed in relation to scaffold microstructure, pore size, degradation rate, and mechanical properties. In addition, these structural and physicochemical properties are correlated with biological performance, including cell migration, proliferation, and differentiation. Pullulan-based materials are particularly suited for applications requiring extensive chemical tunability, such as injectable hydrogels, bioinks, and multifunctional delivery systems. However, their intrinsic bioinertness and limited mechanical strength generally require combination with complementary components to achieve effective cell adhesion and structural stability. Finally, current processing limitations and future strategies are discussed for translating pullulan-based systems into clinical applications. Full article

The adeno-associated virus (AAV) has become the vector of choice for gene therapy and experimental gene delivery, owing to its non-pathogenic nature and ability to achieve persistent gene expression across diverse tissues. AAV has emerged as a key platform in cellular reprogramming and regenerative medicine, with applications spanning transcription factor delivery for in vivo lineage conversion and tissue repair across the CNS, heart, and musculoskeletal systems. However, significant limitations remain, particularly in the context of induced pluripotent stem cell (iPSC) engineering. We assess barriers to efficient iPSC transduction including receptor-dependent entry deficits and activation of p53-dependent DNA damage responses. Although AAV is widely described as non-integrating, evidence indicates that integration events occur in rapidly proliferating and actively reprogramming cells. Critically, we synthesize evidence that cell-type-specific promoters lose fidelity when paired with neurogenic transgene payloads, a cross-tissue problem not addressed in existing AAV reviews, and that published in vivo reprogramming efficiencies may be substantially confounded by promoter leakage in the absence of formal lineage tracing. These aspects, underrepresented in recent platform-level reviews, are specifically emphasized here as a resource for researchers designing rigorous AAV-based reprogramming and gene therapy strategies. Full article

Breast reconstruction after mastectomy or trauma poses considerable clinical and aesthetic challenges that traditional methods, such as silicone implants and autologous tissue flaps, often insufficiently address. This review analyzes the evolution of biomaterials for breast and soft tissue reconstruction, encompassing conventional ECM-derived scaffolds and acellular dermal matrices, as well as advanced hybrid constructs, injectable smart hydrogels, functionalized biomaterials, and cell-integrated systems incorporating adipose-derived stem cells. Emerging fabrication technologies, including 3D bioprinting, electrospinning, and computational imaging-guided design, are examined for their ability to create patient-specific, vascularized scaffolds with adjustable mechanical and biological characteristics. This review analyzes the scientific basis of soft tissue regeneration, focusing on adipogenesis, angiogenesis, immunomodulation, and extracellular matrix remodeling. The paper further overviews the efficacy of both well-known and new biomaterials, providing a detailed discussion of the translational challenges associated with their clinical application. Despite the substantial recent advancements in the field, comprehensive regenerative breast reconstruction requires ongoing interdisciplinary collaboration and innovation to translate promising preclinical results into safe, effective, and accessible clinical solutions for patients. Full article

Volumetric muscle loss (VML) constitutes a significant clinical challenge, defined by the irreversible loss of skeletal muscle tissue and resulting in persistent functional deficits due to fibrosis, chronic inflammation, and insufficient endogenous regeneration. Existing clinical interventions, such as autologous grafting and free functional muscle transfer, are constrained by donor-site morbidity including infection, pain, suboptimal vascularization, and limited functional integration. Although tissue engineering has advanced considerably, no FDA-approved regenerative therapies currently exist for VML, underscoring a substantial translational gap. This review provides a systems-level synthesis of skeletal muscle repair through integrating fundamental biological processes, such as inflammation, satellite-cell activation, myogenesis, angiogenesis, and neuromuscular junction formation, with recent advances in biomaterials, scaffold engineering, and biofabrication technologies. The analysis addresses how critical scaffold design parameters, including alignment, porosity, stiffness, degradation kinetics, and bioactivity, influence cellular responses and tissue integration. Additionally, emerging strategies such as 3D bioprinting, nanofiber-based architectures, stem cell and exosome therapies, and bio-functional stimulation are evaluated inside a unified mechanobiological framework. This analysis is further extended to the regulatory setting, with emphasis on how scaffold composition, mechanism of action, and degree of biological integration affect classification pathways governed by the U.S. Food and Drug Administration. Most advanced VML therapies are anticipated to be regulated as combination products, which will require rigorous preclinical validation, standardized manufacturing processes, and carefully designed clinical studies. By integrating biological principles, engineering design, and regulatory considerations, this review highlights key opportunities, remaining challenges, and future priorities for the clinical translation of next-generation regenerative strategies for VML. Full article

The tooth is a complex biological organ composed of multiple tissues, including enamel, dentine, cementum and pulp. However, dental disease and tooth loss due to periodontitis, caries, or trauma adversely affect most adults at some time in their lives. Tooth regeneration represents a shift in the dental paradigm from removal to repair to regeneration. Tooth regeneration is an extension of the broader field of regenerative medicine, aiming to restore a tissue defect to its original form and function by using biological substitutes to replace lost teeth or tooth tissue, providing a viable alternative to currently available clinical treatments. A full array of cell sources has been trialled for endodontic regeneration, following the basic premise of tissue engineering, including cells–scaffold–bioactive molecules. Several reports have documented dental pulp-like tissue regeneration, either in vitro or following the transplantation of stem cells. Tooth regeneration follows two unique approaches: cell transplantation and cell homing. Cell transplantation has been the predominant approach, whereas cell homing aims to achieve tissue repair and regeneration of the injury site through the chemotaxis of host endogenous cells. This narrative review explores therapeutically viable tooth regeneration approaches by contrasting cell transplantation and cell-to-scaffold methodologies focussing on the cell–scaffold–bioactive molecule triad. Full article

Hyaluronic acid (HA) is a glycosaminoglycan that is found within the body and has both structural and signaling functions in the extracellular matrix. HA is biocompatible and biodegradable; it has a high water content and binds directly to certain cell-surface proteins. Due to these characteristics, it is considered a promising component for the design of biomaterials for regenerative wound healing. This review covers the most recent findings on the use of HA-based biomaterials in soft tissue repair, while also incorporating earlier, foundational studies relevant to the field, focusing on HA’s characteristics, cellular interactions, design, and preclinical and clinical results. The physicochemical characteristics of HA and their influence on cellular responses and tissue regeneration are discussed to show how material properties can be adjusted for specific therapeutic purposes. There have been great advances in chemically modified composite scaffolds and HA matrices, which offer better mechanical stability and controlled degradation. At the same time, new delivery systems have been built using HA, from nanoparticles to gene delivery platforms and growth factors, and these have given the material an active role as a therapeutic agent rather than just a passive one. This narrative review covers the clinical evidence for the effectiveness of commercial products for acute and diabetic wounds, as well as burns and chronic wounds, and discusses where their use is indicated. In the end, the current limitations of the research and future applications and directions are discussed. Full article